cyclic-gmp and Leishmaniasis--Cutaneous

Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-gamma (IFN-gamma) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-alpha/beta also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.

Topics: Animals; Cells, Cultured; Cyclic GMP; Cytotoxicity, Immunologic; DNA-Binding Proteins; Enzyme Activation; Enzyme Inhibitors; Immunity, Innate; Interferon-gamma; Interferons; Interleukin-12; Janus Kinase 2; Killer Cells, Natural; Leishmania major; Leishmaniasis, Cutaneous; Lysine; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phosphorylation; Protein-Tyrosine Kinases; Proteins; Proto-Oncogene Proteins; Signal Transduction; STAT4 Transcription Factor; Trans-Activators; TYK2 Kinase; Up-Regulation